The objective of this project is to elucidate the natural history and pathophysiology of airways obstructive disease (AOD) by determining, from longitudinal analysis of spirometric data obtained in the population enrolled in the Tucson epidemiologic study of AOD, patterns of changes which lead utlimately to frank airways abnormality and by detailed physiological assessment of subjects identified as exhibiting evidence of or susceptibility to AOD. Subjects thus identified will be characterized physiologically. By examining in detail a variety of physiological phenomena, inferences will be drawn regarding structural changes which lead to altered function. Physiological measurements and roentgenographic observations will be correlated to test the hypothesis that enlargement of terminal airspaces is an early structural change which can be brought about by cigarette smoking and which may be an early phenomenon of developing emphysema. The rate of fall of transcutaneous oxygen tension will be assessed as a test to detect this enlargement of airspaces. The CO diffusing capacity test will also be assessed as a test for detecting early AOD and the closing volume test, performed approximately 10 years ago in this population, will be reexamined for its prognostic value. Healthy middle-aged smokers and age/sex matched non-smokers who had detailed physiological studies will be restudied after a 5 year time interval to determine the effects of cigarette smoking per se on lung structure and function. Blood samples will be obtained on the above described selected subjects to examine the role of such biochemical phenomena as specific IgE on the natural history of AOD.